Leffler began his career racing midget cars in the USAC series, where he won three consecutive midget championships from 1997 and 1999, as well as the Silver Crown series championship in 1998. He was the third driver to win three consecutive midget car championships.[1] He won the Hut Hundred and Belleville Nationals in 1997, and the Turkey Night Grand Prix and Copper Classic in 1999.[1] He won his second Turkey Night Grand Prix in 2005.

Leffler made his first, and only, start in the Indianapolis 500 in 2000. This effort was put forth by Treadway Racing with backing from Roger Penske's United Auto group. Leffler qualified in the 17th position, which was also where he finished.

During the 2000 season, Leffler drove full-time for the No. 18 MBNA sponsored Joe Gibbs Racing team in the Busch Series. He finished twentieth in the final standings, earned three pole positions during the year, and finished second at Phoenix. He also made two IRL starts, among them a start for Treadway in the Indianapolis 500 where he started and finished seventeenth. After that season he moved up to the Winston Cup Series to become the driver of the #01 Cingular Wireless Dodge for Chip Ganassi Racing as the permanent replacement for Kenny Irwin, Jr., who was killed in a practice crash while driving for the same team at New Hampshire in 2000. Leffler's car retained sponsorship from BellSouth through its Cingular Wireless property, and with Ganassi's purchase of a stake in Felix Sabates' former team came a switch in manufacturer as Leffler became one of several drivers to drive Dodge Intrepids in the brand's return to NASCAR. It was a controversial decision, as Leffler performed poorly the season prior in excellent Joe Gibbs equipment in the Busch series. During his inaugural Cup season, he had only one top 10 finish and four failures to qualify. He was, however, the inaugural pole setter at Kansas Speedway. After his 37th-place finish in the 2001 championship, Ganassi replaced him with Jimmy Spencer for the 2002 season and remade Leffler's former car into the #41 Target Dodge.

Leffler joined Ultra Motorsports in 2002 to drive the #2 Carquest/Team ASE Dodge Ram in place of the departed Scott Riggs and had great success early on with the team. In his first year, he tied a single season Craftsman Truck Series record by scoring eight pole positions, and qualified no worse than eighth at any race during the season. Despite not winning a race, he had six second-place finishes and a fourth-place finish in the championship. He also won the Night Before the 500 midget race and got to drive Ultra's #7 car in the final two races of the Cup Series season after the team fired Casey Atwood. Leffler finally broke through in 2003 when he scored his first career victory at Dover.

Leffler in the No. 32, racing at Daytona in 2006

Despite the success, Leffler ended up losing his ride at Ultra in controversial fashion. Haas CNC Racing, which was fielding its first full-time Cup Series team, had fired its driver Jack Sprague after the Tropicana 400. Team owner Gene Haas named John Andretti as his replacement, but he was unavailable for the Brickyard 400 due to a prior commitment with Dale Earnhardt, Inc.. Haas approached Leffler to drive the #0 NetZeroPontiac Grand Prix in the race and he agreed to do so. Ultra, which had warned Leffler that such a move would be in violation of his contract, responded by firing him.

Leffler made ten starts in the #0, becoming the permanent driver after the Sirius Satellite Radio at the Glen. The team then signed Ward Burton away from Bill Davis Racing to take over the car, and he joined the team before the season was over to get a head start. Leffler was moved to the #00 Haas Automation car in the Busch Series for the remainder of 2003, with the idea that he would remain there for 2004. At Nashville Superspeedway in 2004, Leffler scored his first career Busch Series victory. He was running third in the points when the team released him from his contract. He ended up finishing twelfth in the championship despite missing the last seven races.

Shortly after his dismissal, Leffler signed a deal to re-join Joe Gibbs Racing for 2005, taking over a newly created Cup team sponsored by FedEx. The No. 11 Chevrolet was regularly outside of the top 35 in points, meaning that it was not guaranteed a starting spot for all races; Leffler was unable to qualify for the Coca-Cola 600 because of it. He was replaced by Terry Labonte for the two road-course races and, eventually, was fired from JGR after nineteen starts in which he failed to record a top ten finish. He was replaced by a mix of Labonte and JGR developmental drivers J.J. Yeley and Denny Hamlin, the latter of whom took over the car full-time the following season.

While racing with Gibbs, Leffler briefly raced with Braun Racing in the Busch Series, a team that had lost their regular driver, Shane Hmiel, to a drug suspension. After leaving Gibbs, Leffler joined Braun Racing on a full-time basis for the remainder of the season. Leffler had scored four top ten finishes with Braun in nine starts for the team.

During the 2007 season, Leffler won the pole for the Winn-Dixie 250 at Daytona International Speedway. He finished ninth. Leffler would make NASCAR history July 28, 2007 as he passed Greg Biffle with two laps remaining to win the Busch Series Kroger 200 at O'Reilly Raceway Park. The win marked the first race victory for a Toyota Camry in Busch Series competition, and the first win for a foreign manufacturer in a top-tier NASCAR series since Al Keller won in a Jaguar in 1954. The win also marked Leffler's second career Busch Series win and first win since the 2004 season. Leffler returned to Sprint Cup in 2008 for a few races in the No. 70 Haas CNC Chevy while driving full-time for Braun Racing's No. 38 Toyota Camry.

In 2009 at the July Daytona race weekend it was announced that the No. 38 Toyota car would be shared with Kasey Kahne for the 2010 NASCAR Nationwide Series season. Leffler remained in the Great Clips Toyota in 2010 and 2011. In late 2011 he was informed that he was free to pursue other opportunities for the 2012 season.

On January 9, 2012, Kyle Busch Motorsports announced that Leffler would drive the No. 18 truck for fourteen races with sponsorship from Dollar General.[2] However, strings of bad luck and poor finishes plagued the team, and Leffler was released on August 14.[3]

Leffler instantly lost consciousness in the accident. When it was found that Leffler was not breathing, the rest of the race was cancelled and victory lane ceremonies did not take place. He was airlifted by helicopter to Crozer-Chester Medical Center in Chester, Pennsylvania,[9] where he was pronounced dead at 9:00 PM EDT, 30 minutes after the accident.[10] An autopsy report stated that the cause of death was a severe blunt force neck and backbone injury.[11]

After his death, many drivers and racing associations such as NASCAR and IndyCar made statements on the death and gave their condolences. NASCAR drivers competing in the 2013 Quicken Loans 400 had special stickers placed on their cars in honor of Leffler. Denny Hamlin, who replaced Leffler in the No. 11 FedEx Toyota in late 2005 had his car repainted to resemble Leffler's livery.[12]

Leffler was the son of Charles and Patricia Leffler. Leffler had a son, Charlie Dean, with Alison East, who was five years old at the time of his death. He shared his life with live-in girlfriend Julianna Patterson;[13] they resided in North Carolina. Leffler was engaged at the time of his death to Julianna Patterson.